Upregulated PXDNL promotes invasive breast carcinoma progression.

BACKGROUND

Invasive breast carcinoma (BRCA) is a common and serious malignancy in women. Peroxidase-like (PXDNL) is associated with poor prognosis in various cancers but has an unclear role in BRCA progression.

METHODS

Bioinformatic analysis of datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UALCAN investigated a potential carcinogenic role of PXDNL, focusing on its correlation with prognosis, promoter methylation, immune cell infiltration, immune checkpoint genes, and relevant biologic functions and pathways.

RESULTS

PXDNL demonstrated a significant expression profile in BRCA, with considerable diagnostic and prognostic implications. Its up-regulation correlated with decreased survival rates across various molecular subtypes of BRCA. Patients in the high PXDNL expression group showed reduced presence of multiple infiltrative immune cell types, including CD8+ T cells, cytotoxic cells, T cells, B cells, dendritic cells (DC), immature dendritic cells (iDC), natural killer (NK) cells, NK CD56bright cells, NK CD56dim cells, and follicular helper T cells (TFH). Additionally, a significant correlation was observed between PXDNL expression and immune checkpoint genes. Gene Set Enrichment Analysis (GSEA) further indicated that high PXDNL expression triggers pathways such as epithelial-mesenchymal transition and protein secretion, while suppressing crucial processes including allograft rejection, IL6-JAK-STAT3 signaling, TNFα signaling via NFκB, adipogenesis, oxidative phosphorylation, DNA repair, and the P53 pathway.

CONCLUSION

Overexpression of PXDNL is associated with poor prognosis and is linked to immune cell infiltration in BRCA. Thus, PXDNL may be a biomarker or therapeutic target for BRCA.